Abstract
An electrospray ionization fast flow technique has been employed to study reactions with CH~3~OD and ND~3~, respectively, of the protonated pentapeptide leucine enkephalin, and of protonated tri‐ and tetrapeptides that make up its backbone structure. Deconvolution of the experimental mass spectral data follod by simulation of the kinetic data by solution of differential equations leads to sets of apparent and site‐specific rate constants. On a time scale of several milliseconds, leucine enkephalin undergoes with ND~3~ four fast H/D exchanges and one slow exchange. Three equivalent exchanges are observed that are ascribed to the protonated amine group at the N‐terminus. Contrary to leucine enkephalin, some of the smaller peptides that do not have tyrosine at the N‐terminus are reactive with CH~3~OD, but the reactions are more than two orders of magnitude slower than the ND~3~ reactions. These peptides do not sequester the ionizing proton at the N‐terminus. The present study demonstrates the capabilities of a fast flow technique in studying gas phase reactions of small biomolecules. It forms part of an effort to understand gas phase conformational changes in proteins through hydrogen‐exchange electrospray ionization mass spectrometry. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33: 707–714, 2001